1. Technical Field
The invention relates to methods and materials involved in determining the severity of a rheumatoid arthritis condition.
2. Background Information
Rheumatoid arthritis (RA) affects individuals in the prime of their life and is feared because of its potential to cause chronic pain and irreversible damage of tendons, ligaments, joints, and bones. The symmetrical involvement of small peripheral joints has an enormous impact on hand and foot functions and poses therapeutic challenges that cannot be easily overcome by joint replacement. Also, systemic manifestations of RA are not rare and can range from relatively minor problems, such as rheumatoid nodules, to life-threatening organ disease.
In addition, RA is a systemic inflammatory disease that primarily manifests itself as synovial inflammation of diarthrodial joints. The typical histopathological changes include dense infiltration of the synovial membrane by mononuclear cells, neoangiogenesis, and hypertrophy and hyperplasia of the synovial lining (Harris (ed); Rheumatoid Arthritis, Philadelphia, WB Saunders Co., pp.3-212 (1997); and Hale and Haynes: Pathology of rheumatoid arthritis and associated disorders. Arthritis and Allied Conditions. A textbook of Rheumatology. Edited by Koopman. Baltimore, Williams and Wilkins, pp.993-1016 (1997)). The etiopathogenesis of the syndrome is not well understood. Several lines of evidence support a central role of T lymphocytes in the disease-specific pathogenic events (Todd et al., Science, 240:1003-1009 (1988); Panayi et al., Arthritis Rheum., 35:729-735 (1992); and Goronzy and Weyand, Rheum. Dis. Clin. North Am., 21:655-674 (1995)). An alternative hypothesis, namely, that macrophages are the pivotal cell type in rheumatoid synovitis, has also been proposed (Firestein and Zvaifler, Arthritis Rheum. 33:768-773 (1990); and Burmester et al., Arthritis Rheum., 40:5-18 (1997)). Whether only T cells or only macrophages or both are the causative elements in RA remains a matter of controversy (Feldmann et al., Cell, 85:307-310 (1996); and Fox, Arthritis Rheum., 40:598-609 (1997)).
RA is primarily a clinical diagnosis. Symmetrical joint involvement, dominant manifestations in peripheral joints, rheumatoid factor production, and the formation of rheumatoid nodules are considered when the diagnosis is made (Arnett et al., Arthritis Rheum., 31:315-324 (1988)). The histological appearance of the synovium varies quite extensively. In addition, no information is available on the mechanisms underlying the topographical arrangement of the inflammatory infiltrate in the rheumatoid synovium.
The invention involves evaluating arthritis conditions. Specifically, the invention provides methods and materials related to determining the severity of an arthritis condition in a mammal. The term xe2x80x9carthritis conditionxe2x80x9d as used herein refers to an infective, autoimmune, or traumatic inflammatory condition that affects a joint. Arthritis conditions can be acute or chronic. A chronic arthritis condition is referred to as rheumatoid arthritis (RA).
RA conditions range from mild to severe. Typically, a patient with a mild rheumatoid arthritis condition experiences pain, swelling, heat, and loss of joint function to a lesser extent than a patient with a severe rheumatoid condition. In addition, patients with sever RA can have one or more germinal centers in an affected joint. A germinal center is a site where B cells proliferate, leading to an increased immune response.
The methods and materials described herein can be used to identify arthritis patients that have either a mild or severe arthritis condition. The ability to distinguish between mild and severe arthritis conditions can help alleviate pain in patients with arthritis by providing appropriate treatments in a timelier manner. In addition, the invention provides methods and materials that can be used to assist medical or research professionals in determining the severity of an arthritis condition. With this assistance, medical or research professionals can assess the treatment needs of arthritis patients with greater accuracy, improving the prognosis of the disease.
In general, the invention features a method for determining the severity of an arthritis condition in a patient. The method includes determining whether or not a sample from the mammal contains an elevated level of a CD21L polypeptide, where the presence of the elevated level indicates that the arthritis condition is severe. The arthritis condition can be rheumatoid arthritis. The sample can be a tissue sample (e.g., a synovial tissue sample). The presence or absence of the elevated level can be determined by measuring a CD21L polypeptide or a CD21L mRNA.
In another embodiment, the invention features a method for determining the severity of an arthritis condition in a mammal. The method includes determining whether or not a sample from the mammal contains an elevated level of a lymphotoxin-xcex2 polypeptide, where the elevated level indicates that the arthritis condition is severe.
Another embodiment of the invention features a method for determining the severity of an arthritis condition in a patient. The method includes determining whether or not a sample from the mammal contains an elevated level of a chemoattractant polypeptide, where the elevated level indicates that the arthritis condition is severe. The chemoattractant can be a B-lymphocyte chemoattractant polypeptide.
Another embodiment of the invention features a method for determining the severity of an arthritis condition in a mammal. The method includes determining whether or not a sample from the mammal contains at least one marker, the marker being an elevated level of a CD21L polypeptide, an elevated level of a lymphotoxin-xcex2 polypeptide, or an elevated level of a chemoattractant polypeptide, where the presence of the at least one marker indicates that the arthritis condition is severe. The arthritis condition can be rheumatoid arthritis. The mammal can be a human. The sample can be a tissue sample (e.g., a synovial tissue sample). The at least one marker can be the elevated level of a CD21L polypeptide. The at least one marker can be the elevated level of a lymphotoxin-xcex2 polypeptide. The at least one marker can be the elevated level of a chemoattractant polypeptide. The chemoattractant can be a B-lymphocyte chemoattractant polypeptide. The method can include determining whether or not the sample contains at least two of the markers. The method can include determining whether or not the sample contains at least three of the markers. The method can include determining whether or not the sample contains at least four of the markers.
In another embodiment the invention features a method of assisting a person in determining the severity of an arthritis condition in a patient. The method includes (a) determining whether or not a sample from the patient contains an elevated level of a CD21L polypeptide, and (b) communicating information about the presence or absence of the elevated level in the sample to the person, where the presence of the elevated level indicates that the arthritis condition is severe. The person can be a medical or research professional. The person can be a doctor, a nurse practitioner, a research scientist, or a research technician. The arthritis condition can be rheumatoid arthritis. The sample can be a tissue sample (e.g., a synovial tissue sample). The communication can include sending the information directly to the person. The communication can include sending the information indirectly to the person. The communication can include making the information electronically available to the person.
Another embodiment of the invention features a method of assisting a person in determining the severity of an arthritis condition in a patient. The method includes (a) determining whether or not a sample from the patient contains an elevated level of a lymphotoxin-xcex2 polypeptide, and (b) communicating information about the presence or absence of the elevated level in the sample to the person, where the presence of the elevated level indicates that the arthritis condition is severe.
Another embodiment of the invention features a method of assisting a person in determining the severity of an arthritis condition in a patient. The method includes (a) determining whether or not a sample from the patient contains an elevated level of a chemoattractant polypeptide, and (b) communicating information about the presence or absence of the elevated level in the sample to the person, where the presence of the elevated level indicates that the arthritis condition is severe. The chemoattractant polypeptide can be a B-lymphocyte chemoattractant polypeptide.
Another embodiment of the invention features a method of assisting a person in determining the severity of an arthritis condition in a mammal. The method includes (a) determining whether or not a sample from the mammal contains at least one marker, the marker being an elevated level of a CD21L polypeptide, an elevated level of a lymphotoxin-xcex2 polypeptide, or an elevated level of a chemoattractant polypeptide, and (b) communicating information about the presence or absence of the at least one marker in the sample to the person, where the presence of the at least one marker indicates that the arthritis condition is severe. The person can be a medical or research professional. The person can be a doctor, a nurse practitioner, a research scientist, or a research technician. The arthritis condition can be rheumatoid arthritis. The mammal can be a human or rodent. The sample can be a tissue sample (e.g., a synovial tissue sample). The at least one marker can be the elevated level of a CD21L polypeptide. The at least one marker can be the elevated level of a lymphotoxin-xcex2 polypeptide. The at least one marker can be the elevated level of a chemoattractant polypeptide. The chemoattractant polypeptide can be a B-lymphocyte chemoattractant polypeptide. The communication can include sending the information directly to the person. The communication can include sending the information indirectly to the person. The communication can include making the information electronically available to the person. The method can include determining whether or not the sample contains at least two of the markers. The method can include communicating information about the presence or absence of the at least two markers in the sample to the person. The method can include determining whether or not the sample contains at least three of the markers. The method can include communicating information about the presence or absence of the at least three markers in the sample to the person. The method can include determining whether or not the sample contains at least four of the markers. The method can include communicating information about the presence or absence of the at least four markers in the sample to the person.
In another aspect, the invention features a kit containing at least two oligonucleotide primer pairs, where each of the primer pairs amplifies a different target nucleic acid sequence, where the target nucleic acid sequence is a CD21L nucleic acid, a lymphotoxin-xcex2 nucleic acid, or a B-lymphocyte chemoattractant nucleic acid.
In another embodiment, the invention features an article of manufacture containing at least two oligonucleotide primer pairs and a label or package insert indicating that each of the at least two oligonucleotide primer pairs can amplify a different target sequence in an amplification reaction, where each target sequence is a CD21L nucleic acid, a lymphotoxin-xcex2 nucleic acid, or a B-lymphocyte chemoattractant nucleic acid.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.